Insight into modulating osteoarthritis progression: lncRNAs and TGF-β/Smad signalling pathway

Long non-coding RNAs (lncRNAs) are a class of non-coding RNA molecules with a length of more than 200 nucleotides that play key roles in the regulation of gene expression and cell physiology. Studies have shown that lncRNAs can participate in the regulation of the TGF-β/Smad signalling pathway by sponging miRNAs or directly activating Smad protein phosphorylation. The TGF-β/Smad signalling pathway has become a key signalling pathway in osteoarthritis (OA), a traditional degenerative joint disease characterised by an imbalance between cartilage degradation and repair. This review systematically discusses the molecular mechanisms by which lncRNAs regulate OA cartilage repair through the TGF-β/Smad signalling pathway, as well as the regulatory roles of these lncRNAs in inflammatory response, extracellular matrix (ECM) homeostasis, and chondrocyte apoptosis. In addition, the article also summarised the clinical transformation strategies based on lncRNA, including nanoparticle delivery systems (such as exosomes and hydrogels), gene editing technologies (such as CRISPR-Cas9), and precision treatment guided by dynamic biomarkers. Although lncRNA therapy still faces challenges in terms of targeted delivery efficiency and specificity, its potential in early diagnosis and regenerative therapy of OA provides a theoretical basis for the development of novel intervention methods. In the future, combining cutting-edge technologies such as artificial intelligence, single-cell sequencing, and 3D organoids, the application of lncRNA regulatory networks is expected to open up new avenues for OA treatment.